胶质母细胞瘤是高度侵袭性和化疗耐药性的癌症，使得它们很难治疗。慢性炎症是胶质母细胞瘤进展的主要驱动因素，因为它促进了炎症途径（如NF-κB信号通路）的异常激活，从而推动癌细胞的侵袭和血管生成。NF-κB因子通常与其自身家族成员二聚体化，但新兴证据表明它们与其他致癌因子的杂交相互作用会促进新靶基因的转录和功能。在这里，我们展示了非经典NF-κB激活直接调节ETS1启动子中的p52，激活其表达。这以一种胶质母细胞瘤特异性的方式影响了ETS1的基因组和转录谱。我们进一步证明，增强的非经典NF-κB信号通路促进p52和ETS1的共定位，导致非NF-κB和非ETS胶质母细胞瘤促进基因的转录激活。我们得出结论，p52诱导的胶质母细胞瘤细胞ETS1过表达重塑了p52和ETS1的全基因组调节网络，从而在转录水平上推动了癌症的进展。 ©2023年，作者。

Gliomas are highly invasive and chemoresistant cancers, making them challenging to treat. Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-κB signalling, which drives cancer cell invasion and angiogenesis. NF-κB factors typically dimerise with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors has been reported to promote transcription of new target genes and function. Here, we show that non-canonical NF-κB activation directly regulates p52 at the ETS1 promoter, activating its expression. This impacts the genomic and transcriptional landscape of ETS1 in a glioma-specific manner. We further show that enhanced non-canonical NF-κB signalling promotes the co-localisation of p52 and ETS1, resulting in transcriptional activation of non-κB and/or non-ETS glioma-promoting genes. We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression.© 2023. The Author(s).